1. Field of Invention
The present invention is directed to improved methods for characterizing materials such as trabecular bone.
2. Discussion of Related Art
A major component of the human musculoskeletal system is bone, which supports our body weight, facilitates motion, and plays critical roles in mineral homeostasis and production of blood cells. Osteoporosis is a disorder of the skeleton in which bone strength is abnormally weak and susceptible to fractures from minor trauma. Regions of the human body for which the risk is greatest include the spine, hips and legs. In the United States, about 30 million people have osteoporosis and almost 19 million more have low bone density. Approximately 700,000 vertebral fractures, 250,000 hip fractures and 200,000 distal radius fractures occur annually in the United States, and billions of dollars are expended each year for the care of osteoporosis in the U.S. Therapeutic treatments of osteoporosis are under intense development.
Clinical assessment of osteoporosis presently relies mainly upon bone mineral density (BMD) measurements. Two common techniques clinically used to determine BMD are dual X-ray absorptiometry (DXA) and ultrasound. DXA measures the absorption of X-rays by the bone tissue, mostly by calcite minerals. In DXA, X-ray irradiation at two different energies is employed to distinguish the X-ray absorption of bone from that of soft tissue. The amount of absorption provides a measure of bone density. DXA is currently the gold standard in osteoporosis screening. Ultrasound measures speed and attenuation of sound waves in bone to predict BMD. However, the error associated with this technique can be significantly larger than that associated with DXA.
A drawback of BMD measurements is that the measured BMD is a gross average quantity and gives no information about either the structural integrity or the mechanical properties of the bone. While there is some correlation of bone mineral density with mechanical strength (the property determining fracture risk), there is a significant variation around the average correlation. For example, in FIG. 1, there is illustrated a graph of a relationship between bone strength and BMD for a set of excised human trabecular bone specimens. Apparent modulus (in MPa), a measure of the bone strength, is represented on the vertical axis, and apparent density (BMD) is represented on the horizontal axis. Line 102 illustrates a correlation between the two quantities. As can be seen in FIG. 1, there is an extensive spread of bone strength at a given density. While a definite correlation between BMD and fracture occurrence exists, it is also clear that densitometry alone does not entirely predict the risk of fracture. This is because the details of the trabecular bone structure (e.g., the “bone quality”) and its evolution over time also contribute significantly to the strength of the bone and thus to the risk of fracture.
It is generally believed that bone microstructure, also referred to as bone quality, may have a significant impact on bone strength. Several medical imaging techniques, such as nuclear magnetic resonance (NMR), magnetic resonance imaging (MRI) and microscopic computed tomography (μCT) have been used to extract structural information about bone samples. μCT is one example of a microscopic imaging technique. Through a series of X-ray radiographs acquired at different orientations, a three-dimensional image of the bone matrix may be constructed. This technique may be used to create an image with voxel resolution as fine as a few μm. A “voxel” is three-dimensional measure of resolution, analogous to the two-dimensional “pixel.” Compared to DXA, μCT is more sensitive to detecting bone loss, but at the expense of requiring a much higher X-ray dosage and is not currently viable for clinical use.
NMR and high-resolution MRI studies of bone in vitro and in vivo have been conducted in the research community. Bone is a highly (˜80%) porous medium consisting of a calcified solid matrix with soft marrow, fat, microvasculature and water filling the pore space. The MRI image of bone is actually the signal of the marrow space because the solid bone tissue does not produce much MRI signal under standard clinical conditions. Three-dimensional images of bone with resolutions of 56 μm have been obtained from small samples. Results of such MRI imaging have included a wide range of topological properties that correlate with bone strength of the sample. In vivo imaging is presently at a resolution above 100 μm and sophisticated subvoxel processing has been tested to further enhance the resolution. From this direct measurement of bone structure, topological parameters can be derived which theoretically and empirically relate to bone strength. However, high resolution MRI is currently limited to the wrist and has not been applied to hip or spine.
Another property from which MR methods derive structural sensitivity is the difference in magnetic susceptibility between the solid and intervening tissue/fluids. When the static magnetic field required for the NMR measurement is applied, this susceptibility contrast gives rise to spatial variations of the magnetic field within the pore space. For example, the broadening (1/T2′) of the resonance line due to the magnetic susceptibility contrast between the bone matrix and the intervening marrow can be measured. This broadening depends on the bone architecture, which in turn may provide a correlation of bone strength. The contribution of the static field inhomogeneity (1/T2′) to the total NMR linewidth (1/T2*) has been measured in vitro and in vivo for a variety of bone samples and subjects, and has been found to correlate with strength parameters such as Young's modulus of elasticity. However, (1/T2′)-based measurements have not yet reached the point of routine clinical use.